Preclinical Evaluation of ⁶⁴Cu-LNTH-1363S to Detect Cardiac FAP-Positive Fibroblasts Using PET Imaging

Area of Science:

• Cardiovascular Research
• Medical Imaging
• Molecular Biology

Background:

• Fibroblast activation protein-expressing (FAP+) fibroblasts play a key role in cardiac remodeling following injury or disease.
• Accurate detection of FAP+ fibroblasts is crucial for understanding and managing heart conditions.

Purpose of the Study:

• To evaluate the efficacy of a novel positron emission tomography (PET) tracer, 64Cu-LNTH-1363S, for detecting FAP+ fibroblasts.
• To assess the tracer's performance in preclinical models of myocardial infarction (MI).

Main Methods:

• Utilized permanent left anterior descending coronary artery ligation and echocardiography-guided ischemia reperfusion models in mice.
• Assessed targeting efficiency of 64Cu-LNTH-1363S through in vivo studies.
• Confirmed in vivo targeting specificity using competitive receptor blocking and autoradiography.

Main Results:

• 64Cu-LNTH-1363S demonstrated sensitive and specific detection of FAP+ cells in both MI models.
• Kinetic modeling revealed a higher distribution volume of the tracer in the infarct zone compared to remote myocardium.
• The tracer successfully visualized FAP+ fibroblasts in the injured heart tissue.

Conclusions:

• Established the feasibility of using 64Cu-LNTH-1363S for noninvasive detection of FAP+ fibroblasts in MI mouse models.
• Provided preclinical evidence supporting the potential of this PET tracer for human studies.
• Highlighted the tracer's utility in assessing cardiac remodeling and injury in various cardiac conditions.